It was found that the natural vinblastine (X) which is an alkaloid extracted from catharanthus roseus has a strong cancerocidal effect and currently used as a remedy for vicious lymphoma or ciliary tumor (Reference Document A). Further, aiming the development of novel medicines, various derivatives making vinblastine as a lead compound are investigated and synthesized (Reference Document B). However, in the present conditions, the syntheses of the most of these derivatives depend on partial syntheses from natural vinblastine or analogues thereof. There is a limitation in the chemical transformation of the natural compound, and it is impossible to investigate the wide and systematic structure-activity relationships. For the effective and systematic synthesis of the derivatives, it is necessary to establish the effective total synthesis of vinblastine. Vinblastine (X) can be considered as a bisindole compound generated by bonding two indole units, vindoline and carbomethoxyvelbanamine (Y).

Therefore, it is important to establish the method for synthesis of each indole unit. However, in the synthesis of the compound composing vindoline unit which is said one compound, the sufficient supplement of vindoline so as to synthesize said vinblastine effectively was not established. In said circumstance, the inventor of the present invention already proposed the effective method for (−)-vindoline (JP application No. 2000-335349 filed on Nov. 7, 2000). Still more, as another problem, the problem that even if the compound (Y) is used as the compound to lead the other indole unit (called as the upper unit) into which vindoline is introduced, sometimes the reaction proceeds with opposite stereoselectivity, is reported (Reference Document C).

Therefore, it is not possible to accomplish the above desired subject, namely, to synthesize vinblastine derivatives effectively, unless the indole derivative which composing the upper unit into which vindoline can be introduced with the desired stereoselectivity is designed and the method for total synthesis of the derivative is established.
Regarding the design of the indole derivative which composing the upper unit, Schill et al reported that vindoline can be introduced with the desired stereoselectivity, when a compound (Z) possessing an eleven-membered ring obtained by ring opening of piperidine ring is used (Reference Document D).

However, since the process to obtain the above eleven-membered ring compound is very complicated, the synthesis of vinblastine using compound (Z) is far from an effective synthetic method from the view point of yield.
The subject of the present invention is based on the knowledge of the above mentioned report by Schill et al, and is intending, (1) to establish an effective and highly stereoselective synthetic method of an upper unit, and to provide a method capable of synthesizing the upper unit derivative (2) with high flexibility to synthesize various vinblastine analogous, and (3) where control of the stereochemistry at the introduction of vindoline is improved. For the purpose to accomplish the above mentioned subjects, the inventors of the present invention have tried to combine the method for synthesis of indole (Reference Document E) using a radical ring forming reaction of thioanilide developed by the inventors of the present invention and the method for synthesis of middle and large ring compound (Reference Document F) using intramolecular alkylation of 2-nitrobenzenesulfonamide. In said investigation, it has become clear that the compound which forms said upper unit can be synthesized under relatively mild conditions when above mentioned reactions are used by combination. Therefore, it is possible to make various functional groups coexist in each reactant when these reactions are used by combination, and said basic subjects of (1) and (2) are dissolved.